First-in-Human, Double-Blind, Randomized Controlled Trial of an Oral Dose of GnRH Antagonist TU2670 in Healthy Women

Author:

Han Sungpil1ORCID,Cho Yong-Soon1,Yoon Seok-Kyu1,Lim Kyoung Soo2,Cho Sang-Heon3,Kim JaeWoo4,Choe Sangmin5,Jung Jinah6,Ghim Jong-Lyul7,Choi SangKeun8,Lee Minhee9,Kim Seon Mi9,Kim Hun-Taek9,Lim Hyeong-Seok1,Yoon Shim Jae10,Bae Kyun-Seop1ORCID

Affiliation:

1. Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea

2. Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea

3. Department of Clinical Pharmacology, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea

4. Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea

5. Department of Clinical Pharmacology and Therapeutics, Pusan National University Hospital, Busan, Republic of Korea

6. Department of Clinical Pharmacology and Therapeutics, Inje University Busan Paik Hospital, Busan, Republic of Korea

7. Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea

8. SK Chemicals, Seongnam, Republic of Korea

9. TiumBio, Seongnam, Republic of Korea

10. Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea

Abstract

Abstract Objective To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TU2670, a novel orally active, nonpeptide gonadotropin-releasing hormone (GnRH) antagonist administered to healthy female participants. Methods This was a first-in-human, multicenter, phase 1, randomized, double-blind, placebo-controlled, single-dose ascending trial that took place in multiple medical centers. A total of 16 healthy premenopausal women (23 to 45 years of age) were randomized and received 20, 40, 80, and 160 mg TU2670 (GnRH antagonist) or placebo 7 days (±1 day) after the onset of menstrual bleeding. We performed a noncompartmental analysis for pharmacokinetic parameters and calculated relative minimum concentration values (Cmin, % Baseline) of serum pharmacodynamic (PD) markers (luteinizing hormone [LH], follicle-stimulating hormone [FSH], and estradiol). Results There were no significant differences among treatments with respect to vital signs, electrocardiography, adverse events, ovulation test results, and ultrasonography. The median Tmax of TU2670 occurred 0.75 to 1.00 hours after dosing, and concentrations then declined, with a mean apparent half-life (t1/2) of 3.0 to 5.9 hours. AUClast (17.7-417.9 ng·h/mL) and Cmax (8.1-95.4 ng/mL) increased in a dose-dependent manner. The PD analysis after a single administration of TU2670 revealed dose-dependent suppression of LH, FSH, and estradiol. Maximal suppression of the pre-dose baseline (%) was 58% to 82% at 6 to 8 hours for LH, 28% to 39% at 6 to 12 hours for FSH, and 34% to 82% at 12 to 24 hours for estradiol. Conclusion The single administration of TU2670 in healthy premenopausal women was well tolerated and resulted in the dose-dependent suppression of LH, FSH, and estradiol, suggesting rapid and significant inhibition of pituitary and ovarian hormones.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference11 articles.

1. Gonadotropin-releasing-hormone-receptor antagonists;Huirne;Lancet.,2001

2. Endometriosis: pathogenesis and treatment;Vercellini;Nat Rev Endocrinol.,2014

3. A peek into the drug development scenario of endometriosis - A systematic review;Goenka;Biomed Pharmacother.,2017

4. Advances in pharmacotherapy for treating endometriosis;Tafi;Expert Opin Pharmacother.,2015

5. An overview of early drug development for endometriosis;Leone Roberti Maggiore;Expert Opin Investig Drugs.,2016

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Experimental and new investigational drugs for the treatment of uterine fibroids;Expert Opinion on Investigational Drugs;2024-04-17

2. Evaluation and management of endometriosis;Climacteric;2023-04-13

3. The latest advances in the pharmacological management of endometriosis;Expert Opinion on Pharmacotherapy;2022-03-01

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3